The overall objectives of this research proposal are to investigate the roles of gastrointestinal hormones in the digestive processes. We now have available specific and sensitive radioimmunoassay systems for gastrin (all forms), big gastrin (PG-34), secretin, gastric inhibitory polypeptide (GIP), cholecystokinin, vasoactive intestinal peptide (VIP), and glucagon. We will continue to conduct studies to develop and validate specific radioimmunoassays for bombesin, somatostatin, motilin, and growth hormones. We will use these assay systems to study the temporal pattern of release of gastrointestinal hormones after various stimuli. We plan to study the effects of a single hypothalamic or hypophyseal hormone on the release of gastrointestinal hormones in normal and hypophysectomized rats and dogs. Similar studies will be performed in normal, hypophysectomized and acromegalic man. We will continue our studies designed to determine the pattern of release and tissue levels of different molecular forms of gastrin, CCK and secretin in animals, in normal man and in patients with duodenal ulcer disease (before and after operation). We will study the influence of diseases on the patterns of release of gastrointestinal hormones: specifically, gastrin in Zollinger-Ellison syndrome, VIP in pancreatic cholera and secretin in normal and duodenal ulcer patients. We plan to correlate biologic activity of gastrointestinal hormone (CCK, glucagon, GIP, VIP and big gastrin) with direct measurements of their circulating concentrations by radioimmunoassay. We plan to continue to study the mechanisms (organ and cellular) by which gastrointestinal hormones are catabolized. We plan to study the synthesis of gastrointestinal hormones in cell cultures (ZE tumors, VIP tumors) by incorporation of labeled amino into hormones and by radioimmunoassay of culture media. We will investigate the binding of different hormones to target tissue with emphasis upon developing receptor type assays for gastrointestinal hormones. We will determine the storage pattern of individual gastrointestinal hormones in segments of gastrointestinal mucosa and the ability of different agents to stimulate or inhibit the release of gastrointestinal hormones from segments of the gut.